This invention relates generally to mass spectrometers, and in particular to a reflectron type time-of-flight mass spectrometer and to a glass reflectron lens for such a spectrometer wherein the lens has a gradient electrical resistance on its surface.
Mass spectrometers are analytical instruments capable of identifying unknown materials in complex mixtures with precision in the parts per billion range. Once used exclusively in research laboratories, mass spectrometers are now in use in a broad range of applications. They are used in screening for pesticides in canned foods, controlling semiconductor manufacturing processes, diagnosing disease, exploring for natural resources, discovering new pharmaceuticals, predicting volcano eruptions, and security systems. Indeed, these instruments have traveled beyond our world aboard the Galileo and Cassini spacecrafts to provide atmospheric analysis of neighboring worlds within our solar system.
Time of Flight Mass Spectrometry (TOF-MS) is rapidly becoming the most popular method of mass separation in analytical chemistry. The development of low cost digitizers and extremely fast ion detectors has fueled this popularity. TOF-MS is easily deployed and can produce very high mass resolution. This technique of mass separation can be adapted for many forms of sample introduction and ionization. Unlike quadrupoles and ion traps, time of flight mass analyzers perform well with very high mass molecules of the type frequently found in protean applications. Wiley and McLaren in 1955, followed by Cotter in 1992, and Wollnik in 1993 have described time of flight mass analyzers.
Time-of-flight mass spectrometers are produced in two main types: linear instruments and reflectron instruments.
Linear Time of Flight Mass Spectrometers
FIG. 1 illustrates a linear time of flight mass spectrometer embodied as a matrix assisted laser desorption ionization (MALDI) instrument 100. In a linear time of flight mass spectrometer, an unknown sample is first converted to ions. The sample is deposited on a plate 102. A light beam from a laser 104 is directed at the sample on plate 102 which causes the sample to ionize. The resultant ions are injected into a flight tube 106 wherein they travel towards the ion detector 108. The detector may be embodied as a microchannel-plate type detector as described in U.S. Pat. No. 6,828,729, the entire disclosure of which is incorporated by reference.
The motion of the ions within the flight tube can be described by the following equation.t2=m/z(d2/2Vse)In Equation 1, m/z is the mass to charge ratio of the ion, d is the distance to the detector, and Vse is the acceleration potential.
The lighter ions (i.e. ions having relatively lower masses) travel toward the detector 108 faster than the higher mass ions. If the flight tube is long enough, the ions will arrive at the detector according to their mass, i.e., lowest to highest.
When the ions arrive at the detector 108, they initiate a cascade of secondary electrons within the detector, which results in the generation of a series of very fast voltage pulses. The voltage pulses precisely signal the arrival of the ions. A high-speed oscilloscope or transient recorder is used to record the arrival times. FIG. 2 illustrates the arrival time spectrum of a sample of Brandykinin analyzed on a linear time of flight mass spectrometer. Knowing the exact arrival times, Equation 1 can be used to solve for the mass-to-charge ratios of the ions.
Reflectron-Type Time of Flight Mass Spectrometer
The second type of time-of-flight mass spectrometer is the reflectron instrument. FIG. 3 illustrates a known arrangement of a reflectron TOF mass spectrometer 300. The reflectron design takes advantage of the fact that the further the ions are allowed to travel, the greater the distance between ions of slightly differing masses. Greater distances between ions with different masses will increase the arrival time differences between the ions and thereby increase the resolution at which ions having similar mass-to-charge ratios (m/z) can be differentiated. In addition, the reflectron design corrects for the energy dispersion of the ions leaving the source.
In the reflectron analyzer 300, the ions are injected into the flight tube 302 in the same manner as in a linear instrument described above. The ions travel down the flight tube and enter the reflectron lens 304. FIG. 4 shows the construction of a known reflectron lens. It consists of a plurality of stacked metal rings that are spaced and insulated from each other. An electrostatic field is created within the reflectron lens 304 by applying different high voltage potentials to each of the metal rings. The electrostatic field has a polarity that causes the ions to decelerate and eventually reverse their direction. The ions exit the lens 304 and are directed to the ion detector 306. The action of the reflectron lens on the ions effectively doubles their length of travel in the flight tube. The additional travel time improves mass resolution without adding additional length to the flight tube.
Most time of flight instruments manufactured today incorporate reflectron lenses. As shown in FIG. 4 a reflectron lens consists of a stack of precision ground metal rings 402 alternating with insulating spacers 404. The rings and spacers are held together with threaded rods 406. The reflectron lens assembly may have hundreds of components which must be carefully assembled and aligned (typically by hand) in a clean, dust free environment. Additionally, a voltage divider must be included in each row or layer in order to produce the electrostatic field gradient necessary to reverse the direction of the ions.
An improved variant of the classical reflectron lens design utilizes a single resistive glass tube to generate the gradient electric field. A resistive glass tube reflectron lens is shown in FIG. 5. The monolithic structure of the resistive glass tube replaces the multi-component assembly of the metal ring type of reflectron lens.
Reflectron lenses fabricated from resistive glass tubes have thus far been produced with a uniform resistance along the inside of the tube. That architecture is useful for many reflectron geometries. However, a significant performance advantage and greater design flexibility could be realized if the electrical resistance varied discretely or continuously along the length of the lens.
Resistive glass reflectron lenses are fabricated from lead silicate glass that has been subjected to a hydrogen reduction process to produce a thin resistive layer on the inside surface of the tube. A resistive glass reflectron lens is described in U.S. Pat. No. 7,154,086, the entire disclosure of which is incorporated herein by reference.
The hydrogen reduction process consists of loading the glass tube into a closed furnace through which pure hydrogen or a controlled mixture of hydrogen and oxygen is purged. The temperature is gradually increased, typically at a rate of 1-3 degrees per minute. Beginning at approximately 250° C., a chemical reaction occurs in the glass in which the lead oxide in the glass converts to a semi-conductive state. This reaction occurs in the first few hundred angstroms of the cross section of the glass. As the glass continues to be heated in the presence of the hydrogen, more of the lead oxide is chemically reduced, thereby providing lower electrical resistance. Temperature, time, gas pressure, and gas flow can be controlled to provide a desired amount of electrical resistance on the surface of the glass.
The electrical resistance is also dependent on the composition of the glass. For example, a glass containing more lead oxide with a modifier such as bismuth can be used to produce lower resistances. The hydrogen reduction process makes all surfaces of the glass tube conductive. Unwanted conductive surfaces can be stripped by chemical or mechanical means.
A known hydrogen reduction process has the following parameters:
3 hour ramp up from RT to 200° C.;
1 hour ramp up from 200 to 300° C.;
12.5 hour ramp up from 300 to 445° C.;
hold at 445° C. for 3 hours in hydrogen at a pressure of 34 psi and a hydrogen flow of 40 l/m.
The reduction temperature is limited on the low end by the minimum temperature needed to sustain the reaction and is limited on the high side by the sag point of the glass.
In some applications, it is desirable to produce a segmented resistive tube in which certain sections of the tube have significantly different values of electrical resistance. In other applications it is desirable to have a continuous resistance gradient in which the resistance along the wall varies continuously along the length of the tube. The variation may be linear or nonlinear. For example, an orthogonal geometry time of flight mass spectrometer utilizes a reflectron tube having a nonlinear resistance characteristic. U.S. Pat. No. 7,081,618, the entire disclosure of which is incorporated herein by reference, and U.S. Pat. No. 7,154,086 describe methods to produce a uniform electrical resistance in a lead silicate glass tube by subjecting the tube to a reducing environment within a hydrogen furnace.